Publication: Histopathology of Duchenne muscular dystrophy in correlation with changes in proteomic biomarkers
Authors
Zweyer, Margit ; Sabir, Hemmen ; Dowling, Paul ; Gargan, Stephen ; Murphy, Sandra ; Swandulla, Dieter ; Ohlendieck, Kay
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-403
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info:eu-repo/semantics/article
Description
Abstract
Duchenne muscular dystrophy is an inherited
disorder of early childhood that affects multiple systems
in the body. Besides late-onset cardio-respiratory
syndrome and various body-wide pathophysiological
changes, X-linked muscular dystrophy is primarily
classified as a disorder of the skeletal musculature. This
is reflected by severe histopathological alterations in
voluntary contractile tissues, including progressive fibre
degeneration, fat substitution, reactive myofibrosis and
chronic inflammation. The underlying cause for
dystrophinopathy are genetic abnormalities in the DMD
gene, which can result in the almost complete loss of the
membrane cytoskeletal protein dystrophin, which
triggers the collapse of the dystrophin-associated
glycoprotein complex and disintegration of sarcolemmal
integrity. This in turn results in an increased frequency
of membrane micro-rupturing and abnormal calcium ion
fluxes through the impaired plasmalemma, which
renders muscle fibres more susceptible to enhanced
proteolytic degradation and necrosis. This review
focuses on the complexity of skeletal muscle changes in
X-linked muscular dystrophy and outlines cell biological
and histological alterations in correlation to proteomewide variations as judged by mass spectrometric
analyses. This includes a general outline of sample
handling, subcellular fraction protocols and modern
proteomic approaches using gel electrophoretic and
liquid chromatographic methods for efficient protein
separation prior to mass spectrometry. The proteomic
profiling of the dystrophic and highly fibrotic diaphragm
muscle is described as an example to swiftly identify
novel proteomic markers of complex histopathological
changes during skeletal muscle degeneration. The
potential usefulness of new protein markers is examined
in relation to key histopathological hallmarks for
establishing improved diagnostic, prognostic and
therapy-monitoring approaches in the field of
dystrophinopathy.
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